Author + information
- Miguel Valderrábano, MD∗ ()
- ↵∗Address for correspondence:
Dr. Miguel Valderrábano, Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6550 Fannin Street, Suite 1901, Houston, Texas 77030.
Left atrial appendage (LAA) closure devices have emerged as alternatives to oral anticoagulation (OAC). In the United States, Watchman (Boston Scientific, Marlborough, Massachusetts) obtained U.S. Food and Drug Administration approval after showing an overall all-stroke prevention equivalence with warfarin in the PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL-AF (Evaluation of the Watchman Left Atrial Appendage Closure Device in Patients With Atrial Fibrillation Versus Long-Term Warfarin Therapy) trials (1,2). Its main competing device, the Amulet (Abbott Laboratories, Abbott Park, Illinois) and its predecessor Amplatzer Cardiac Plug (Aga Medical, Golden Valley, Minnesota), have been approved in the European Union, based on nonrandomized registry data (3,4). A randomized trial is underway. Other devices are at different stages of development and clinical testing.
LAA closure has since gained rapid acceptance and has shown dramatic growth in procedural volumes. An exponential growth in LAA closure device implantations has occurred since the 2015 U.S. Food and Drug Administration approval of Watchman.
There is a plethora of data supporting the procedural safety of these devices that was obtained from post-approval studies (5). However, there are also important gaps of knowledge. The pathway toward Watchman U.S. Food and Drug Administration approval chosen by the manufacturer’s decision makers was via randomized comparisons with warfarin. Whereas this approach is scientifically sound, by design, it studied the device’s performance in a patient population different to the one the Watchman was meant to target: patients unsuitable for long-term OAC, who were specifically excluded in order to be randomizable. The trials’ design also excluded patients with competing, nonatrial fibrillation (non-AF) risks of stroke such as extensive atheromatous aortic plaque or significant shunting via a patent foramen ovale. In short, the Watchman was tested and validated in a patient population different to that in which it is used. It would not be surprising if outcomes in real-life use differ to those in the clinical trials.
The real-life use of LAA occlusion unavoidably includes implantations in patients who do not complete the post-implantation OAC regime (warfarin and aspirin for 45 days, followed by aspirin and clopidogrel for 4.5 months) and that have coexisting, non-AF-related risks of stroke.
Thus, a first concern arises: Is LAA occlusion of any value for patients that have AF as well as other competing stroke risks? For example, patients with complex atheromatous aortic plaque as well as AF benefit from OAC because it protects against both LAA and atheroembolic thrombogenesis. LAA occlusion alone would leave the latter mechanism unprotected. We do not have evidence-based support for Watchman stroke protection in these patients.
Second, it has become clear that both Watchman and Amulet have a significant risk of device-related thrombus, that is, the development of a clot on the surface of the device, which is subject to embolization and stroke. This is a huge drawback of the technology because it represents iatrogenesis at its worst: creating the very problem it is meant to prevent. If a device-related thrombus (DRT) is diagnosed, OAC is mandatory; if the patient had contraindications, we have created a serious problem.
In this issue of JACC: Clinical Electrophysiology, Alkhouli et al. (6) write a systematic review of DRT associated with LAA occlusion devices. Recent series (7) and reanalysis of PROTECT and PREVAIL data (8) support the idea that DRT is not a negligible event after LAA occlusion, and that when it happens, it quadruples the risk of stroke. In this meta-analysis of the published data (6) reports an overall incidence of DRT of about 4% and when present, it is associated with an increased risk of stroke (4- to 5-fold).
Alkhouli et al. (6) address a very important issue and provides confirmation of DRT as an ever present but small risk, as validated by a global look at the published data. They illustrate the temporal development of DRT as anywhere in the first year, disputing the value of 45-day transesophageal echocardiography only as a reliable surveillance strategy. Temporal peaks in incidence—such as those at 45-, 90-, 180-, and 365-days post-implantation—are probably a reflection of the times in which imaging with transesophageal echocardiography was performed and do not reflect the chronology of the DRT pathogenesis. Some DRT-associated factors were consistently found, such as previous strokes, advanced age, or high CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age ≥75 Years, Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack or Thromboembolism, Vascular Disease, Age 65 to 74 Years, Sex) scores, but these are neither surprising nor particularly helpful to the clinician because they are not modifiable and do not necessarily change the indications for LAA occlusion. Other factors, such as deep implants or large device size, are more nebulous and could not be found consistently across studies.
Where do we go from here? Clearly, LAA occlusion can provide a solution for stroke prevention in many AF patients. But it is also evident that more data are needed to understand the optimal patient selection, imaging surveillance, and post-implantation treatment in order to avoid DRT and its associated risk of stroke.
↵∗ Editorials published in JACC: Clinical Electrophysiology reflect the views of the authors and do not necessarily represent the views of JACC: Clinical Electrophysiology or the American College of Cardiology.
Dr. Valderrábano has received honoraria for serving as a Watchman proctor for Boston Scientific; served as a consultant for LifeTech and St. Jude Medical; and has received research support from Biosense Webster.
The author attests he is in compliance with human studies committees and animal welfare regulations of the author’s institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
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